Device and method for safe location and marking of a cavity and sentinel lymph nodes

ABSTRACT

A subcutaneous cavity marking device percutaneously implantable in breast tissue during a biopsy procedure. The marking device including at least two implantable bodies, one made from a first material and another made from a second material wherein the first and second materials are different materials and the at least two implantable bodies are adapted to be inserted into a subcutaneous cavity created by removal of tissue. The at least two implantable bodies are detectable via non-invasive techniques as tissue cavity markers and at least one of the at least two detectable bodies is an electronic chip connected to the other of the at least two implantable bodies.

RELATED APPLICATION

This application is a continuation-in-part of U.S. Ser. No. 09/347,185,filed Jul. 2, 1999, which is a continuation-in-part of U.S. Ser. No.09/285,329, filed Apr. 2, 1999, which is a continuation in part of U.S.Ser. No. 09/220,618, filed Dec. 24, 1998.

FIELD OF THE INVENTION

This invention is directed to subcutaneous cavity and sentinel nodemarking devices, delivery devices, and methods. More particularly, acavity marking device, delivery device, and method are disclosed thatenable one to determine the location, orientation, and periphery of thecavity by radiographic, mammographic, echographic, or other noninvasivetechniques. The cavity marking device typically is made up of one ormore resilient bodies and a radiopaque or echogenic marker. Alsodisclosed are a composition and method for noninvasively locating thesentinel lymph node in a mammalian body to determine if cancerous cellshave spread thereto.

BACKGROUND OF THE INVENTION

Over 1.1 million breast biopsies are performed each year in the UnitedStates alone. Of these, about 80% of the lesions excised during biopsyare found to be benign while about 20% of these lesions are malignant.

In the field of breast cancer, stereotactically guided and percutaneousbiopsy procedures have increased in frequency as well as in accuracy asmodem imaging techniques allow the physician to locate lesions withever-increasing precision. However, for any given biopsy procedure, asubsequent examination of the biopsy site is very often desirable. Thereis an important need to determine the location, most notably the center,as well as the orientation and periphery (margins) of the subcutaneouscavity from which the lesion is removed.

For example, in cases where the lesion is found to be benign, a visual,noninvasive follow-up examination of the biopsy site is often performedto ensure the absence of any suspect tissue and the proper healing ofthe cavity from which the tissue was removed. Such follow-up examinationis also performed where the lesion is found to be malignant and thephysician is confident that all suspect tissue was removed and thetissue in the region of the perimeter or margins of the cavity is“clean”.

In some cases, however, the physician may be concerned that the initialbiopsy failed to remove a sufficient amount of the lesion. Furthermore,in some percutaneous biopsy procedures, such as those using theMammotome biopsy probe, it is very difficult to guarantee clean margins.Such a biopsied lesion is colloquially referred to as a “dirty lesion”or “having a dirty margin” and requires follow-up observation of anysuspect tissue growth in the surrounding marginal area of the initialbiopsy site. Thus, an excision around the original biopsy site mustoften be performed. In such a case, the perimeter of the cavity shouldpreferably be identified, as the cavity may contain cancerous cells.Identification of the cavity perimeter is desirable to avoid the risk ofopening the cavity, which could release and spread the cancerous cells.Moreover, the site of the re-excised procedure itself requires follow-upexamination, providing further impetus for accurate identification ofthe location of the re-excised site. Therefore, a new marker may beplaced after re-excision.

Prior methods of marking biopsy cavities utilize one or more tissuemarking clips as the biopsy site-marking device. Most commonly, thesemarker clips have a “horseshoe” configuration. The marker clips attachto the walls of the cavity when the free ends or limbs of the“horseshoe” are pinched together, trapping the tissue. This device hassignificant drawbacks.

For instance, prior to placing the marker clip at the cavity site, caremust be taken to remove residual tissue debris, typically by vacuum, tominimize the possibility that the marker clip attaches to any loosetissue as opposed to the cavity wall. Once the cavity is prepared, theclip must be examined to ensure that the limbs of the clip aresubstantially straight. If the limbs have been prematurely benttogether, the clip will be discarded, as it will most likely not attachproperly to the cavity wall. Actual placement of the clip often requiresadditional vacuum of the cavity wall to draw the wall into the aperturebetween the limbs of the marking clip so that a better grip is obtainedbetween the limbs of the clip. Additionally, there is always thepossibility that the clip may detach from the cavity wall during orafter withdrawal of the tools used to place the clip into the cavity.

Aside from the problems inherent in the placement of the marking clip,there are also limitations associated with how well the marking clip canidentify a biopsy cavity. As the marking clip must trap tissue forproper attachment, in cases of endoscopic, fluoroscopic, or blindplacement, the clip can only be placed on a wall of the cavitysubstantially opposite to the opening of the cavity.

Moreover, patient concern limits the number of clips that may be placedin a cavity. As a result, the medical practitioner is forced to identifythe outline of a three dimensional cavity by a single point as definedby the marking clip. Obviously, determination of the periphery of abiopsy cavity from one point on the periphery is not possible.

These limitations are compounded as the biopsy cavity fills within a fewhours with bodily fluids, which eventually renders the cavity invisibleto noninvasive techniques. Another difficulty in viewing the clip stemsfrom the fact that the clip is attached to the side, not the center, ofthe cavity. This makes determining the spatial orientation and positionof the cavity difficult if not impossible during follow-up examination.Additionally, during a stereotactic breast biopsy procedure, the breastis under compression when the marking clip is placed. Upon release ofthe compressive force, determining the location of the clip can beunpredictable, and any information once known about the orientation andlocation of the periphery of the cavity is lost.

The marker clip does not aid in the healing process of the biopsy wound.Complications and false information may arise if the marker strays fromits original placement site. As described above, if a re-excision of thesite is required, the marker clip may also interfere when excision of atarget lesion is sought.

Other devices pertaining to biopsy aids are directed to assisting in thehealing and closure of the biopsy wound, but they do not address theclinical need or desire of accurately preserving the location andorientation of the biopsy cavity. See, e. g., U.S. Pat. Nos. 4,347,234;5,388,588; 5,326,350; 5,394,886; 5,467,780; 5,571,181; and 5,676,146.

In cases where a biopsy excises lesion or tumor is suspected to becancerous, it is desirable to determine whether any cancerous cells havespread from the site of the original lesion or tumor. A sentinel node(SN) is the first lymph node to receive drainage of lymphatic fluid andcells from a tumor or malignant growth. For various cancers such asmalignant melanoma and breast cancer, identification of the SN is now astandard technique for determining whether cancerous cells have migratedto a lymph gland from the site of the original lesion or tumor.Increasing data suggests that the status of the SN may predict whetherother nodes in the axilla (i. e. the armpit) harbor cancerous cells.Although identification of the SN may be desirable after some biopsyprocedures, there are occasions where identification of the SN isdesirable even though no biopsy procedure is performed. In fact, athorough analysis of multiple sections (0.5-mm intervals) of a sentinelnode or nodes is more likely to detect hidden micrometastases than aroutine single-section examination of many regional nodes, including thesentinel node, according to Jannink et al. in “Serial Sectioning ofSentinel Nodes in Patients with Breast Cancer: A Pilot Study,” Annals ofSurgical Oncology, 5 (4): 310-314.

Thus, accurately determining the location of a SN, permits removal ofthe SN to determine its pathology. If the SN does not contain cancerouscells, the cancer has not spread and the stage of the cancer can bedetermined. The ability to make this determination from an examinationof the SN minimizes the number of lymph nodes removed and eliminates theneed to remove additional lymph nodes. In a review in Breast Diseases: AYear Book Quarterly Vol. 10 No. 3, of a paper by Hack et al., “Physicaland Psychological Morbidity After Axillary Lymph Node Dissection forBreast Cancer,” J Clin Oncol 17: 143-149, 1999, Vetto states thatapproximately 27% of patients undergoing sentinel lymph node biopsy forearly-stage breast cancer still require axillary lymph node dissection(ALND) due to the existence of a positive node. Accordingly, theremaining 63% of the patients could benefit by an SN biopsy and avoidhaving radical dissection.

Previously, it was impossible to locate the sentinel node withoutperforming ALND. In the case of breast cancer, determining whether thecancerous cells migrated involved removal of all axillary lymph nodes.This required radical surgery. This painful option often lead tocomplications that resulted in significant morbidity and even mortality.As discussed by Hack et al., pain and discomfort after ALNDsignificantly corresponded to quality of life after the procedure.According to Hack et al., patients with more than 13 lymph nodesdissected reported more pain than women with fewer lymph nodesdissected.

More recently, a technique known as “sentinel node biopsy” allowed foraccurate mapping of a SN's location by the use of blue dye and aradioactive tracer, separately or in combination. Typically, a dyeand/or a radioactive tracer are injected around the location of a tumor,into the biopsy cavity or tumor cavity (if the tumor was partially orcompletely removed), or “subdermally” into the parenchymal tissueanterior to the tumor. This latter technique is described by De Cicco etal. (1999) in “Lymphoscintigraphy and Radioguided Biopsy of the SentinelAxillary Node in Breast Cancer,” J Nucl Med 39: 2080-2084, 1998, and ina review of that article by Haigh et al. (1999) in Breast Diseases: AYear Book© Quarterly, Vol. 10 No 3. The dye migrates from the tumor sitethrough the lymphatic channels to the regional lymph nodes that servethe cancerous tissue. The SN, which is the node most likely to beinvolved with cancer, is identified through surgery and removed forpathologic analysis. When a radioactive tracer is used, a gamma probe orlike-device is used to further assist a physician in identifying thesite of the SN.

Unfortunately, visualization of the blue dye depends upon the surgeonlocalizing it, and no preoperative assessment of mapping is possible.Therefore, the surgeon must first make an incision in the generalvicinity of the lymph nodes, then dissect around the area to locate theblue dye. Another complication arises as the dye may cause an allergicreaction in some individuals. This reaction may leave a mark on the skinsimilar to a ‘tattoo.’

Using a radioactive tracer, alone or in combination with blue dye, tolocate the SN also has some disadvantages. It is an interdisciplinaryprocess, requiring nuclear medicine personnel, adherence to radiationsafety regulations, preparation of the radiocolloid, and gamma detectioninstrumentation. Furthermore, the safety of this procedure isquestionable. See e. g., Miner et al. (1999). “Guidelines for the SafeUse of Radioactive Materials During Localization and Resection of theSentinel Lymph Node,” Ann Surg Oncol 6: 75-82.

In the case of a lumpectomy, when the lesion is known to be cancerous,locating the SN is desirable so that the SN is removed in the sameprocedure as the lumpectomy. In fact, even if the pathology of thelesion is not yet known, there are reasons for initiating the SNlocalization during a breast biopsy procedure, as discussed below.

Previously, imaging techniques, such as ultrasound, MRI, and CT,attempted to non-invasively find and diagnose cancerous lymph nodesprior to removing them. However, according to Schlag. (1998). “The‘Sentinel Node’ Concept: More Questions Raised than Answers Provided?”Oncologist 1998; 3 (5): VI-VII, general criteria such as size, shape,structure, or texture in the various imaging modalities are unreliable,and these techniques result in low sensitivity and/or low specificity.As described by Veronesi et al. (1997). “Sentinel-node biopsy to avoidaxillary dissection in breast cancer with clinically negativelymph-nodes,” Lancet June 28; 349 (9069): 1864-7, in 32 (38%) of 85patients with metastatic axillary nodes, the only positive node was thesentinel node. Accordingly, if all of the nodes were checked by imaginginstead of locating and biopsying the SN, the chances of missing thecancer would likely have been much higher. Furthermore, because ofusually low specificity, these techniques require surgical excision andexamination of multiple lymph nodes, many of which may contain nocancer. In contrast, by identifying only one or a few SN's, withouttrying to make any diagnosis of cancer prior to tissue removal, theexcision is much less extensive, yielding a smaller tissue sample. Also,the histological examination of one or a few SN's can be more thoroughthan the case where many lymph nodes require examination.

Therefore, one objective of the invention described herein is to providea marking device, delivery device, and method that enable noninvasivedetermination of cavity location, orientation, and periphery.

Another objective of is to provide an atraumatic marking device thatdoes not rely on pinching or piercing tissue.

Another objective is to provide a method of delivering through a smallopening a marking device for marking the borders of a cavity.

Another objective is to provide a composition and method for localizingand marking a sentinel node.

Another objective is to provide a composition capable of (1) depositionin or around a lesion and migration to and accumulation in theassociated sentinel node, and (2) noninvasive detection.

Another objective is to provide a method for remotely detecting thelocation of a sentinel node with a minimum of trauma and toxicity to thepatient.

Yet another objective is to provide a composition and method for bothmarking a lesion cavity and locating the sentinel node in the sameprocedure.

SUMMARY OF THE INVENTION

This invention relates to devices and procedures for percutaneouslymarking a biopsy or lumpectomy cavity. In particular, the inventivedevice is a biopsy cavity marking body made of a resilient, preferablybioabsorbable material having at least one preferably radiopaque orechogenic marker. The device may take on a variety of shapes and sizestailored for the specific biopsy cavity to be filled. For example, thedevice in its simplest form is a spherical or cylindrical collagensponge having a single radiopaque or echogenic marker located in itsgeometric center. Alternatively, the body may have multiple componentslinked together with multiple radiopaque or echogenic markers.

A further aspect of the invention allows the marker or the body, singlyor in combination, to be constructed to have a varying rate ofdegradation or bioabsorption. For instance, the body may be constructedto have a layer of bioabsorbable material as an outer “shell.”Accordingly, prior to degradation of the shell, the body is palpable.Upon degradation of the shell, the remainder of the body would degradeat an accelerated rate in comparison to the outer shell.

The marking device may additionally contain a variety of drugs, such ashemostatic agents, pain-killing substances, or even healing ortherapeutic agents that may be delivered directly to the biopsy cavity.Furthermore, the material and configuration of the sponge itself may behemostatic. Importantly, the device is capable of accurately marking aspecific location, such as the center, of the biopsy cavity, andproviding other information about the patient or the particular biopsyor device deployed.

The marking device is preferably, although not necessarily, deliveredimmediately after removal of the tissue specimen using the same medicalinstrument used to remove the tissue specimen itself. Such medicalinstruments are described in U.S. Pat. Nos. 5,111,828; 5,197,484;5,353,804; 5,511,566; 5,546,957; 5,560,373; 5,817,033; pending U.S.patent application Ser. No. 09/145,487, filed Sep. 1, 1998 and entitled“PERCUTANEOUS TISSUE REMOVAL DEVICE”; and pending U.S. patentapplication Ser. No. 09/184,766, filed Nov. 2, 1998 and entitled“EXPANDABLE RING PERCUTANEOUS TISSUE REMOVAL DEVICE”. The marking deviceis compressed and loaded into the delivery device and percutaneouslyadvanced to the biopsy site where, upon exiting from the deliverydevice, it expands to substantially fill the cavity from the biopsy. Thephysician may then use follow-up noninvasive detection techniques, suchas x-ray mammography or ultrasound, to identify, locate, and monitor thebiopsy cavity site over a period of time.

The marking device is usually inserted into the patient's body eithersurgically via an opening into the body cavity, or using a minimallyinvasive procedure employing such medical instruments as a catheter,introducer, biopsy probe, or similar device, or a specially-designeddelivery device used alone or in conjunction with a catheter,introducer, biopsy probe, or similar device. When inserted via theminimally invasive procedure, the resiliency of the body allows themarking device to be compressed upon placement in a delivery device.Upon insertion of the cavity marking device into the cavity, theresiliency of the body causes the cavity marking device to self-expand,substantially filling the cavity. Following expansion, the markingdevice volume following expansion preferably is 3 to 30 times itscompressed volume, and more preferably 5 to 22 times, and mostpreferably about 10 times. The resiliency of the body can be furtherpredetermined so that the body is palpable, thus allowing tactilelocation by a surgeon in subsequent follow-up examinations. Typically,the filler body is required to be palpable for approximately 3 months.However, this period may be increased or decreased as needed.

The expansion of the resilient body can be aided by the addition of abiocompatible fluid, which is absorbed into the body. For instance, thefluid can be a saline solution, a painkilling substance, a healingagent, a therapeutic fluid, or any combination of such fluids. The fluidor combination of fluids may be added to and absorbed by the body of thedevice before or after deployment of the device into a cavity. Forexample, the body of the marking device may be presoaked with the fluidand then delivered into the cavity. In this instance, the fluid aids theexpansion of the body of the device upon deployment. Another example isprovided as the device is delivered into the cavity without beingpresoaked. In such a case, fluid is delivered into the cavity after thebody of the device is deployed into the cavity. Upon delivery of thefluid, the body of the device soaks up the fluid, thereby aiding theexpansion of the cavity marking device as it expands to fit the cavity.The fluid may be, but is not limited to being, delivered by the accessdevice. Furthermore, expansion of the body of the marking device may beaided by body fluids, such as the fluid component of blood, alreadypresent in the cavity.

By “biocompatible fluid” what is meant is a liquid, solution, orsuspension that may contain inorganic or organic material. For instance,the biocompatible fluid is preferably saline solution, but may be wateror contain adjuvants such as medications to prevent infection, reducepain, or the like. Alternatively or additionally, the fluid may be usedto mark the sentinel lymph node, as will be described later. Obviously,the liquid is intended to be a type that does no harm to the body.

After placement of the cavity marking device into the cavity, thebioabsorbable body degrades at a predetermined rate. As the body of thecavity marking device is absorbed, tissue is substituted for thebioabsorbable material. Moreover, while the body degrades, the marker,which is usually suspended substantially in the volumetric center of thebody of the device, is left in the center of the cavity. Thus, during asubsequent examination, a medical practitioner having knowledge of thedimensions of the body of the cavity marking device can determine thelocation as well as the periphery of the biopsy cavity. The orientationof the cavity is self-evident as the marker is left in substantially thecenter of the cavity. For the case where multiple markers are used, themarkers are usually placed in a manner showing directionality.

The body, marker, or radiopaque or echogenic coatings can be made todegrade in situ and be absorbed into the patient's body over apredetermined period of time. It is generally preferred that if themarker's radiopacity or echogenicity is chosen to degrade over time,such degradation does not take place within at least one year afterimplantation of the inventive device. In this way, if a new lump orcalcification (in the case of a breast biopsy) is discovered after thebiopsy, such a marker will allow the physician to know the relation ofsuch new growth in relation to the region of excised tissue. On theother hand, and as discussed below, a bioabsorption period of threemonths is preferred for any such coatings on the perimeter of the bodyitself.

Another variation of the invention is that the body of the markingdevice is formed from a bioabsorbable thread-like surgical material, forexample a suture material. Preferably, the surgical material isresilient. In this variation the surgical material is looped through amarker. The marking device may have any number of loops or any number ofopposing pairs of loops. Another variation of the marking deviceincludes an opposing member on each loop. For example, a loop could befolded to form the opposing member.

This invention further includes the act of filling the biopsy cavitywith a bioabsorbable liquid, aerosol or gelatinous material, preferablygelatinous collagen, allowing the material to partially solidify or geland then placing a marker, which may have a configuration as describedabove, into the center of the bioabsorbable material. The gel may alsobe made radiopaque or echogenic by the addition of radiopaque orechogenic materials, such as powdered tantalum, tungsten, bariumcarbonate, bismuth oxide, barium sulfate or other barium- orbismuth-containing compounds.

This method may be combined with any aspect of the previously describeddevices as needed. For instance, one could insert a hemostatic orpain-killing substance as described above into the biopsy cavity alongwith the bioabsorbable material. Alternatively, a bioabsorbable markercould be inserted into a predetermined location, such as the center, ofthe body of bioabsorbable material.

It is within the scope of this invention that either or both of themarker or markers and the bioabsorbable body may be radioactive,especially if a regimen of treatment using radioactivity iscontemplated.

This procedure may be used in any internal, preferably soft, tissue, butis most useful in breast tissue, lung tissue, prostate tissue, or lymphgland tissue. Obviously, though, treatment and diagnosis of breasttissue problems forms the central theme of the invention.

In contrast to the marker clips as described above, the cavity markingdevice has the obvious advantage of marking the geometric center of abiopsy cavity. Also, unlike the marking clip which has the potential ofattaching to loose tissue and moving after initial placement, themarking device self-expands upon insertion into the cavity, thusproviding resistance against the walls of the cavity thereby anchoringitself within the cavity. The marking device may be configured to besubstantially smaller, larger, or equal to the size of the cavity;however, in some cases the marking device will be configured to belarger than the cavity. This aspect of the biopsy site-marking deviceprovides a cosmetic benefit to the patient, especially when the biopsyis taken from the breast. For example, the resistance provided by thecavity marking device against the walls of the cavity may minimize any“dimpling” effect observed in the skin when large pieces of tissue areremoved, as, for example, during excisional biopsies. The marking devicemay be configured to allow tissue ingrowth, being replaced by tissue asit is absorbed into the patient's body.

The invention further includes a delivery device and method forplacement of a marking device. For example, the invention includes asheath capable of being placed in contact with a cavity, a cartridge orapplicator in which a marking device may be placed, and a disengagingarm onto which the cartridge is mounted. The marking device willpreferably have a frictional fit with the cartridge. Preferably, thesheath is placed in contact with the cavity, for example, simultaneouslywith the biopsy device or soon after the biopsy device obtains a sample.The sheath may be placed at a point of entrance of the cavity or it maybe partially inserted into the cavity. The delivery device cartridge andengaging arm are then inserted into the sheath and advanced into thecavity until a portion of the cartridge containing the marking device ispositioned within the cavity but a portion of the cartridge is stillwithin the sheath. Next, the delivery device cartridge is retractedwhile the disengaging arm prevents the marking device from beingretracted from the cavity. Thus, the marking device remains in thecavity and radially expands to substantially fill the cavity. Hence, themarking device is delivered and expands in the cavity without a need forsimultaneously pushing the marking device into the cavity. Anotheraspect of this invention is that the frictional fit between a markingdevice and a cartridge may be sufficiently increased to minimizepremature placement of the marking device into the cavity.

Other delivery devices and methods for using them are disclosed,including a “sheath-over-probe” device and method and “through-cannula”devices and methods. These devices and methods are well suited to applythe marking device having a body comprising absorbable suture orcollagen and described herein, but could be used with any of the markingdevices in the present application.

The “sheath-over-probe” device includes a sheath that slides over aprobe, such as a biopsy probe. It is well suited for use with theMammotome® 11 GA Probe (now owned by Johnson & Johnson) but may be sizedto fit other commercially available biopsy devices. The sheath isintroduced into the body along with the probe. After obtaining a biopsysample, the probe is removed, leaving the sheath in place. The markingdevice is then delivered through the sheath.

The “through-cannula” device is intended for insertion through thecannula portion of a biopsy device; it, too, is well suited for theMammotome® 11 GA Probe but may be sized to fit other commerciallyavailable biopsy devices.

Although the subcutaneous cavity marking device and methods describedabove are suited for percutaneous placement of the marker within abiopsy cavity it is not intended that the invention is limited to suchplacement. The device and method are also appropriate for intraoperativeor surgical placement of the marker within a biopsy cavity.

The present invention also provides an alternative method to remotelydetect sentinel nodes (SN). This method includes the deposit, preferablyby injection via a thin needle applicator or using a marker deliverydevice described herein, of a remotely detectable contrast agent thatwill migrate to the SN, allowing the exact location of the SN to bepinpointed and targeted for removal using minimally invasive techniques.This method eliminates the need for potentially toxic radioactive tracermaterial. In addition, the lack of toxicity of such agents obviates theneed to remove the lesion and/or the SN on the same day.

These agents may be any biologically compatible agents capable of remotedetection. Examples of such remote detection include, but are notlimited to magnetism such as a magnetometer, Hall effect sensor, ormagnetic resonance imaging (MRI); ultrasound; thermal means; highintensity ultraviolet techniques; fluorescent dye techniques; singly orin combination.

One example of such a contrast agent is an echogenic microsphere capableof reflecting ultrasonic energy. These microspheres, which averagetypically between 0.2 microns and 5 microns in diameter, may be mixedwith a biologically compatible carrier fluid and injected into the bodyin the vicinity of the lesion. Upon an exposure to ultrasonic energy,the spheres reflect the energy creating an ultrasonic reflection. Theultrasonic reflection resulting from a large number of the microspheresthat have accumulated in the SN permits detection of the particular nodeby a conventional ultrasonic probe. Such microspheres are available atvarious pharmaceutical companies such as Acusphere, Sonus, and AlliancePharmaceutical Corp.

Another example of a detectable agent is a biologically compatiblemagnetically detectable body such as a magnetic microsphere. Such amagnetically detectable body can be the echogenic microsphere describedabove that is either fabricated from or coated with a magnetic material.Alternatively, the magnetically detectable body may be a solid or othertype of magnetic body capable of being incorporated into a carrier fluidand deposited around the lesion or its cavity as described above. Thesebodies are preferably capable of migration to and accumulation in the SNso that, in a similar fashion to the echogenic microspheres, thecumulative magnetic field produced by these magnetic bodies allows forlocation of the SN by remote and noninvasive means.

Yet another such contrast agent is a radiopaque fluid or suspensioncontaining radiopaque particles, detectable using X ray, fluoroscopy, orcomputed tomography (CT). Again, this contrast agent is preferablycapable of migration to and accumulation in the SN to enable one tononinvasively determine the location of the SN.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1M illustrate various configurations of the device.

FIG. 1 A illustrates a tissue cavity marking device with a sphericalbody and a single centrally located marker.

FIG. 1 B shows a tissue cavity marking device with a cylindrical bodyand two ring-shaped markers aligned near the cylinder's longitudinalaxis.

FIG. 1 C shows another tissue cavity marking device with a multifaced orirregular body and a single centrally located marker.

FIG. 1 D illustrates a tissue cavity marking device with a body havingpores.

FIG. 1 E is a partial cross-sectional view of FIG. 1D.

Figure IF illustrates a tissue cavity marking device with a body havingan outer shell of a bioabsorbable material.

FIGS. 1 G-1 J illustrate various configurations of the device having abody comprising suture-type material.

FIG. 1 G illustrates a tissue cavity marking device with a number ofloops.

FIG. 1H illustrates a tissue cavity marking device with a pair ofopposing loops.

FIG. 11 illustrates a tissue cavity marking device with two pairs ofopposing loops.

FIG. 1 J illustrates a tissue cavity marking device having a pair ofopposing loops where the loops are longitudinally folded formingopposing members.

FIG. 1 K illustrates a tissue cavity marking device with two pairs ofopposing loops where each loop is longitudinally folded forming opposingmembers.

FIGS. 1 L and 1 M illustrate tissue cavity marking devices having anelongated body having circular or rectangular cross section and ametallic marker band oriented with its axis perpendicular to the longaxis of the body.

FIGS. 2A-2G illustrate various configurations of the marker.

FIG. 3A illustrates a cavity marking device having multiple bodycomponents traversed by a single wire or suture marker, or multiplewires or suture markers.

FIG. 3B illustrates a cavity marking device having a helically woundwire or suture marker.

FIG. 3C illustrates a cavity marking device having wire or suturemarkers on the perimeter of the body.

FIG. 3D illustrates a cavity marking device having wire or markers onthe ends of the body.

FIGS. 4A-4C illustrate a method of marking a biopsy tissue cavity withthe device of the present invention.

FIGS. 4D-4F illustrate a method of marking a biopsy tissue cavity withthe device of the present invention wherein a biocompatible fluid isdelivered to the cavity marking device after placement.

FIGS. 4G-4I illustrate a method of marking a biopsy tissue cavity withthe device of the present invention wherein a biocompatible fluid isused to push the cavity marking device out of the access device and intothe biopsy tissue cavity.

FIGS. 4J-4L illustrate a method of marking a biopsy tissue cavity withthe device of the present invention wherein the body material of themarking device is deposited into the biopsy cavity prior to theplacement of the marker within the biopsy device.

FIGS. 5A-5B illustrate a spherical wire marking device for deploymentwithout a filler body into a tissue cavity.

FIG. 5C illustrates a cylindrical wire marking device for deploymentwithout a filler body into a tissue cavity.

FIGS. 5D-5E illustrate a helical coil wire marking device for deploymentwithout a filler body into a tissue cavity.

FIGS. 6A-6D illustrate a method for marking a biopsy tissue cavity withthe marking device of the present invention wherein the marking deviceexpands into the cavity without the need for simultaneous pushing of themarking device into the cavity.

FIGS. 7A-7K illustrate devices for marking a biopsy tissue cavity withthe marking device of the present invention.

FIGS. 8A-8I illustrate a variation of a delivery device and a method forusing it to deliver a marking device to a tissue cavity made by theprobe of a medical instrument.

FIGS. 9A-9F illustrate a variation of a delivery device and a method forusing it to deliver a marking device to a tissue cavity through thecannula of a medical instrument.

FIGS. 10A-1 OH illustrate another variation of a delivery device andmethod for using it to deliver a marking device to a tissue cavitythrough the cannula of a medical instrument.

FIGS. 11 A-11 E illustrate another variation of a delivery device andmethod for using it to deliver a marking device to a tissue cavitythrough the cannula of a medical instrument.

FIGS. 12A-12C illustrate a method for locating a sentinel node.

FIGS. 13A-13B illustrate a method for marking a biopsy or lumpectomycavity and locating a sentinel node.

DETAILED DESCRIPTION OF THE INVENTION

The following illustrations are examples of the invention describedherein. It is contemplated that combinations of aspects of specificembodiments or combinations of the specific embodiments themselves arewithin the scope of this disclosure.

FIGS. 1 A-1 M show various configurations of a preferred subcutaneouscavity marking device of the present invention. Here the marking device100 is displayed as having either a generally spherical body 102 (FIG.1A), a generally cylindrical body 104 (FIG. 1 B), or a multi-faced orirregular body 106 (Figure I C). In general, it is within the scope ofthis invention for the body to assume a variety of shapes. For example,the body may be constructed to have substantially curved surfaces, suchas the preferred spherical 102 and cylindrical 104 bodies of FIGS. 1Aand 1B, respectively. The body may have conical or ellipsoidal, etc.shapes as well. It is further within the scope of this invention for thebody to have substantially planar surfaces, such as polyhedric (i. e.cubic, tetrahedral, etc.) or prismatic, etc. forms. Finally, the bodymay also have an irregular or random shape, in the case of a gel,combining features of various curved and planar surfaces. Body 106 ofFIG. 1 C is an example of such an irregular body shape. The particularbody shape will be chosen to best match to the biopsy cavity in whichthe device is placed. However, it is also contemplated that the bodyshape can be chosen to be considerably larger than the cavity.Therefore, expansion of the device will provide a significant resistanceagainst the walls of the cavity. Moreover, the aspect ratio of thedevice is not limited to what is displayed in the figures. For example,the cylindrical body 104 may have a shorter or longer length asrequired.

In the bodies of FIGS. 1 A and 1 C, the generally spherical marker 150is located at or near the geometric center of the body. Such aconfiguration will aid the physician in determining the exact locationof the biopsy cavity, even after the body degrades and is absorbed intothe human or mammalian body.

The ring-shaped markers 154 of FIG. 1 B are generally aligned along thelongitudinal axis 114 of body 104. Note that although the ring-shapedmarkers 154 are spatially oriented so that their longitudinal axes liealong the longitudinal axis 114 of the body 104, each marker may assumea wide variety of random or predetermined spatial orientations otherthan the aligned orientation seen in FIG. 1 C. It can be appreciatedthat a nonspherical marker such as marker 154 is useful in aiding aphysician in determining the spatial orientation of the deployedinventive device.

Obviously, markers 150 and 154 may reside in locations other than thosedemonstrated in FIGS. 1 A-1 C. It is, however, preferred that markers150 and 154 dwell in a predetermined, preferably central, location andorientation in the device body so to aid the physician in determiningthe location and orientation of the biopsy cavity. The markers hereindescribed may be affixed to the interior or on the surface of the bodyby any number of suitable methods. For instance, the marker may bemerely suspended in the interior of the body (especially in the casewhere the body is a gel), it may be woven into the body (especially inthe case where the marker is a wire or suture), it may be press fit ontothe body (especially in the case where the marker is a ring or band), orit may affixed to the body by a biocompatible adhesive. Any suitablemeans to affix or suspend the marker into the body in the preferredlocation is within the scope of the present invention.

Tissue regrowth in a particular orientation can also be promoted by abody design shown in Figure ID. Here, body 110 contains a number ofpores 138 through which tissue may grow. The pores may also be alignedin a substantially parallel fashion, traversing the thickness of thebody so that tissue may regrow from one side of the body through to theother side. This is demonstrated in inset Figure I E, which shows aportion 130 of Figure ID in partial longitudinal cross section, completewith pores 138 traversing through the thickness of portion 130. Suchpores 138 can be parallel to each other as shown in FIG. 1 E, or theymay be perpendicularly, radially, or even randomly oriented in thedevice body.

A trio of markers is also shown in FIG. 1 D evenly aligned along thebody longitudinal axis 140. Barb marker 156, spherical marker 150, andring-shaped marker 154 demonstrate the use of different multiple markersin a single body 110. As previously described, such a design helps aphysician to determine the spatial orientation of the inventive devicewhen it is deployed in a biopsy cavity. Although the barb marker 156 isillustrated in a ‘V’ configuration, it is an important aspect of thebarb marker 156 to have a shape that is clearly not spherical. Thisallows the barb marker 156 to be easily distinguished fromcalcifications that may be observed during any noninvasive imagingtechniques.

Figure IF depicts a further embodiment of the present invention in whichbody 112 is enveloped in an outer shell 142 consisting of a layer ofbioabsorbable material such those mentioned above. This configurationallows the perimeter of the biopsy cavity to be marked to avoid exposingthe cavity, in the case of a “dirty” margin where re-excision may benecessary, to remaining cancerous cells as the tissue begins to re-growinto the cavity. Such a shell 142 can be radiopaque and/or echogenic insitu, or it may be augmented with an additional coating of an echogenicand/or radiopaque material. The shell 142 can also be made to bepalpable so that the physician or patient can be further aided indetermining the location and integrity of the implanted inventivedevice.

Shell 142 may be designed to have a varying bioabsorption rate dependingupon the thickness and type of material making up the shell 142. Ingeneral, the shell can be designed to degrade over a period ranging fromas long as a year or more to as little as several months, weeks, or evendays. It is preferred that such a bioabsorbable shell be designed todegrade between two and six months; especially preferred is threemonths. In the design of Figure IF, interior 144 of body 112 may be across-linked, collagenous material that is readily absorbed by the humanor mammalian body once the shell 142 degrades. Interior 144 may befilled with a solid or gelatinous material that can be optionally maderadiopaque by any number of techniques herein described.

As will be described in additional detail with respect to FIGS. 2A-2F,marker 150 in the device shown in Figure IF may be permanentlyradiopaque or echogenic, or it may be bioabsorbable and optionallycoated with a radiopaque and/or echogenic coating that degrades over apredetermined period of time. It is clinically important that the markerremain detectable for at least about one to five years so that thephysician may follow the patient to ensure the health of the tissue inthe vicinity of the biopsy cavity. Especially preferable is a markerwhose radiopacity or echogenicity lasts between about one and threeyears.

Each of the bodies depicted in FIGS. 1A-1F may be made from a widevariety of solid, liquid, aerosol-spray, powder, spongy, or expandinggelatinous bioabsorbable materials such as collagen, cross-linkedcollagen, regenerated cellulose, synthetic polymers, synthetic proteins,and combinations thereof. Also contemplated is a body made from afibrin-collagen matrix, which further prevents unnecessary bleeding, andminimizes the possibility of hematoma formation.

Examples of synthetic bioabsorbable polymers that may be used for thebody of the device are polyglycolide, or polyglycolic acid (PGA),polylactide, or polylactic acid (PLA), poly s-caprolactone,polydioxanone, polylactide-co-glycolide, block or random copolymers ofPGA and PLA, and other commercial bioabsorbable medical polymers.Preferred is spongy collagen or cellulose. As mentioned above, materialssuch as hemostatic and painkilling substances may be incorporated intothe body and marker of the cavity marking device. The use ofhemostasis-promoting agents provides an obvious benefit, as the devicenot only marks the site of the biopsy cavity but aids in healing thecavity as well. Furthermore, such agents help to avoid hematomas. Thesehemostatic agents may include AVITENE Microfibrillar Collagen Hemostat;ACTIFOAM collagen sponge, sold by C. R. Bard Inc.; GELFOAM SterilePowder or Sponge, manufactured by The Upjohn Company (Michigan);SURGICEL Fibrillar from Ethicon Endosurgery, Inc.; TISSEEL VH, asurgical fibrin sealant sold by Baxter Healthcare Corp.; Helistatcollagen sponge from Integra Lifesciences; Helitene absorbable collagenhemostatic agent in Fibrillar form; and polyethylene glycol (PEG) orcollagen/PEG compositions from Cohesion. Such agents also have theuseful property of expanding between 3 and 30 times their compressedvolume upon release into a cavity and/or upon hydration. The device mayalso be made to emit therapeutic radiation to preferentially treat anysuspect tissue remaining in or around the margin of the biopsy cavity.It is envisioned that the marker would be the best vehicle fordispensing such local radiation treatment or similar therapy. Also, thebody itself may be adapted to have radiopaque, echogenic, or othercharacteristics that allow the body to be located by noninvasivetechnique without the use of a marker. Such characteristics permit thepossibility of locating and substantially identifying the cavityperiphery after deployment but prior to absorption of the device. Suchan embodiment may allow delivery in liquid or gel form through a muchsmaller lumen than those marking devices having one of the markerspreviously described. Furthermore, an echogenic coating may be placedover the radiopaque marker to increase the accuracy of locating themarker during ultrasound imaging.

Further, as illustrated in FIGS. 1 G-1K, the device can be deployed as aloosely wound ball or looped arrangement of bioabsorbable surgicalmaterial with a marker placed at the geometric center of the device. Thematerial may be, for example, resilient suture material, that upondeployment into a tissue cavity provides resistance against the cavitywall and allows the marker to be located at substantially the center ofthe cavity. In this variation, suture material may be looped through theband/ring 154; in such a configuration, the suture material acts as thebody of the inventive device. As described elsewhere, the suture maycomprise a bioabsorbable material. The suture material may also haveradiopaque, echogenic, or other characteristics described herein thataid in the noninvasive location of the device. Desirably, the suturematerial 158 is flexible to facilitate the expansion of the filler bodyto fill the cavity. The device may be in the form of multiple passes ofsuture material 158 looped through a marker 154 (FIG. 1 G). The suturematerial may also be configured in the form a pair of opposing loops 160with a marker 154 between the loops 160 (FIG. 1H), or two pairs ofopposing loops 160 with the marker 154 in the center of the device (FIG.11). The opposing loops 160 may be bent longitudinally to form opposingmembers 162 (FIGS. 1J, 1K). The longitudinally bent opposing member 162may be, but is not necessarily, formed by applying heat to the suture toset the “bend”. An aspect of this variation is that the opposing members162 provide resistance against the walls of a delivery device, thereby,minimizing the possibility of the marking device being prematurelyreleased from the delivery device. Upon the desired deployment, theresiliency of the suture will expand the device and provide significantresistance against the walls of the cavity with the opposing members 162providing additional resistance. It is within the scope of thisinvention to optionally deliver a biocompatible liquid, gel, powder, orthe like before, during, or after deployment of a self-centeringsuture-containing device such as those illustrated in FIGS. 1 G-1 K.

FIGS. 1 L and 1M illustrate preferred embodiments of the inventivetissue cavity marking device 182 and 184 each having an elongated body178 or 180 with a circular or rectangular cross section and a metallicmarker band 154. The metallic marker band 154 preferably is orientedwith its axis 174 perpendicular to the long axis 176 of the body 178 or180 to allow maximum compression of the elongated body in the radialdirection. The elongated bodies 178 and 180 preferably comprisecollagen-containing material with hemostasis-promoting properties.

One method of making the marking device 182 or 184, a marker 154 (or anyother marker) may be placed on the edge of a sheet of filler bodymaterial such as gelatin or collagen. The sheet may then be rolled orfolded to form a device having an elongated body 178 or 180 having acircular or rectangular cross section. Alternatively, a block ofcollagen or other filler body material may be cut into a rectangular orcylindrical shape. A needle may be used to create a hole through one endlengthwise, preferably only halfway through. A tube containing a markersuch as marker 154 may be placed into the hole created by the needle,and a plunger used to push the marker out of the tube and into thefiller body, where it may be held in place by friction. Multiple markersmay be used to help provide orientation when visualized in the patienton X ray, ultrasound, etc.

One advantage of the collagen material and some of the other materialsdisclosed herein for the body of the marking device is that it can beeasily cut with scissors, a knife, or a scalpel. Therefore, a physiciancan trim the body of the marking device to fit the cavity during theprocedure. This is especially useful when creating the cavity andplacing the marking device surgically. Furthermore, if re-excision inthe same region is required, the surgeon will have no trouble cuttingthrough the body of the marking device.

FIGS. 2A-2G illustrate various forms of the marker 110. The marker 110may be a sphere 150 (FIG. 2A), a hollow sphere 152 (FIG. 2B), a ring orband 154 (FIG. 2C), a barb 156 (FIG. 2D), a flexible suture or flexiblewire 158 (FIG. 2E), or a crimped tube or a folded strip of material 172(FIG. 2G). Also, the marker may have a distinguishing mark 170 (FIG.2F). As mentioned above, the barb 156 is illustrated in FIG. 2D ashaving a “V” shape. The barb 156 is intended to distinguish the markerfrom calcifications when viewed under noninvasive imaging techniques. Assuch, the barb 156 is not limited to the “V” shape; rather, it has ashape that is easily distinguishable from a spherical or ovalcalcification.

The marker itself may aid in deploying the body. The marker may be madeof a spring material such as superelastic nickel titanium alloy orstainless spring steel for delivery in compression to expand the body tosubstantially fill the cavity. The barb 156 of FIG. 2D and the flexiblewire 158 of FIG. 2E are particularly suited to mechanically aiddeployment of the body (not shown).

The hollow sphere 152 of FIG. 2B is more susceptible to detection byultrasound than the solid sphere 150 of FIG. 2A. For instance, suchspherical markers such as markers 150 and 152 can be beads of silicon orsilicon-containing compounds, such as silicone or Si02. In the case of aring or band marker 154 seen in FIG. 2C, the body of the cavity markingdevice may be woven or placed through the band or ring 154. The markermay also be a wire or suture 158 as shown in FIG. 2E and as discussed ingreater detail below. In such a case, the marker 158 may be affixed tothe exterior perimeter of the body by an adhesive or woven through thebody. Another improvement may arise from the marker wire or suture 158being configured in a particular pattern within the body of the device,e. g., wrapping around the body in a helical manner. As describedelsewhere, the wire or suture 158 may also be configured to comprise thebody of the marking device. In the case of the marker 150 shown in FIG.2F, distinguishing or identifying mark 170 can be in the form of simplemarks as shown, or it may be one or more numbers, letters, symbols, orcombinations thereof. These marks 170 are preferably located in morethan one location on the marker 150 so that the marker may be readilyand simply identified from multiple orientations under a variety ofviewing conditions. Such a mark 170 can be used to identify the patientand her condition, provide information about the marker and body of thetissue cavity marking device, provide information about thecircumstances and date of the implantation, who performed the procedure,where the procedure was performed, etc. In the case of multiple biopsysites, this distinguishing mark 170 permits one to differentiate andidentify each different site. The mark 170 may be applied via any numberof techniques such as physical inscription, physical or plasmadeposition, casting, adhesives, etc. The mark 170 may also be anelectronic chip providing any necessary information in electronic formthat can be remotely detected by appropriate means. The marking devicemay use the device or technology of a Trovan Transponder (ElectronicIdentification Systems—Santa Barbara, Calif.). Medical information mayitself be directly encoded into the device, or a code on the device maybe keyed to a corresponding record in a computerized database containingthe medical information. The medical information may include such dataas a pathology report of a biopsy sample taken from the site beingmarked, and this information may be entered into the computer recordbefore or after implantation of the marking device. Furthermore, thisinformation may be updated as needed. Alternatively or additionally, themark 170 may itself be remotely programmable to add patient or procedureinformation, pathology information, or the like after implantation inthe body, although adding such capability to the marking device mayincrease its size.

An important aspect of the invention is that the marker may beradiopaque, echogenic, mammographic, etc. so that it can be located bynoninvasive techniques. Such a feature can be an inherent property ofthe material used for the marker. Alternatively, a coating or the likecan be added to the marker to render the marker detectable or to enhanceits detectability. For radiopacity, the marker may be made of anonbioabsorbable radiopaque material such as platinum, platinum-iridium,platinum-nickel, platinumtungsten, gold, silver, rhodium, tungsten,tantalum, titanium, nickel, nickel-titanium, their alloys, and stainlesssteel or any combination of these metals. By mammographic we mean thatthe component described is visible under radiography or any othertraditional or advanced mammography technique in which breast tissue isimaged.

As previously discussed, the marker can alternatively be made of orcoated with a bioabsorbable material. In this case, the marker can, forinstance, be made from an additive-loaded polymer. The additive is aradiopaque, echogenic, or other type of substance that allows for thenoninvasive detection of the marker. In the case of radiopaqueadditives, elements such as barium-and bismuth-containing compounds, aswell as particulate radiopaque fillers, e. g., powdered tantalum ortungsten, barium carbonate, bismuth oxide, barium sulfate, etc. arepreferred. To aid in detection by ultrasound or similar imagingtechniques, any component of the device may contain air bubbles or maybe combined with an echogenic coating. One such coating is ECHO COATfrom STS Biopolymers. Such coatings contain echogenic features, whichprovide the coated item with an acoustically reflective interface and alarge acoustical impedance differential. As stated above, an echogeniccoating may be placed over a radiopaque marker to increase the accuracyof locating the marker during ultrasound imaging.

Note that the radiopacity and echogenicity described herein for themarker and the body are not mutually exclusive. It is within the scopeof the present invention for the marker or the body to be radiopaque butnot necessarily echogenic, and for the marker or the body to beechogenic but not necessarily radiopaque. It is also within the scope ofthe invention that the marker and the body are both capable of beingsimultaneously radiopaque and echogenic. For example, if a platinum ringmarker were coated with an echogenic coating, such a marker would bereadily visible under x-ray and ultrasonic energy. A similarconfiguration can be envisioned for the body or for a body coating.

The marker is preferably large enough to be readily visible to thephysician under x ray or ultrasonic viewing, for example, yet be smallenough to be able to be percutaneously deployed into the biopsy cavityand to not cause any difficulties with the patient. More specifically,the marker will not be large enough to be palpable or felt by thepatient.

Another useful version of the invention is shown in FIG. 3A. In thisdevice, there are several cylindrical body members 302; however, thereis no limit to the number of body members that can make up the device.The body members 302 can individually or together take on a variety ofsizes and shapes as discussed above depending on the characteristics ofthe biopsy cavity to be filled. The body members 302 may uniformly or incombination be made of one or more materials suitable for use in abiopsy cavity as previously described.

Here one or more markers may traverse two or more body member segmentsthrough the interior of the body members 302 as shown in FIG. 3A. Here,markers 318 are located substantially parallel to the longitudinal axis320 of each right cylindrical body member 302 in their interior,connecting each body member 302 while marking their geometric center asbetween the markers. Such a marker 318 may be used in conjunction withthe other markers as described above and may also be accompanied by oneor more additional markers arranged randomly or in a predeterminedpattern to variously mark particular sections of the device.Alternately, such a marker may, singly or in combination with othermarkers, be affixed on or near the surface of the sponge so as to markthe perimeter of the body member 302.

Of course, when used in conjunction with other connecting markers,marker 318 need not necessarily connect each body member; it may be usedsolely to indicate the orientation or location of each individual spongeor the entire device, depending on the material, geometry, size,orientation, etc. of marker 318. When not used in this connectingfunction, therefore, marker 318 need not traverse two body members 302as shown in FIG. 3A.

A variety of patterns can be envisioned in which all or part of theperimeter of the sponge body is marked. For example, a marker 322 canwrap around the body 302 in a helical pattern (FIG. 3B), or it can beused in conjunction with other markers 324 in a pattern parallel to thelongitudinal axis 320 of the body 302 (FIG. 3C). Another usefulperimeter marking pattern is shown in FIG. 3D, where marker segments 326are affixed at or near the surface of the circular bases of thecylindrical body 302 in a cross pattern, indicating the ends of thesponge and their center. As seen from the figures, the marker(s) may,but do not necessarily, have some texture. Any marker pattern, internalor external to the body, is within the scope of the present invention.For the applications depicted in FIGS. 3A-3D, it is preferred that themarker be a radiopaque or echogenic wire or suture.

Another possible configuration is obtained by combining the suture orwire markers 158 in a body with any other type marker 150,152,154, or156 or vice versa. For example, in FIG. 3B, a spherical marker 150 maybe placed in the center of the cylindrical body 302. Therefore, thecylindrical body 302 would contain the suture or wire marker 322 wrappedhelically adjacent to the outer perimeter, and a marker 150 would beplaced in the center of the cylindrical body 302. Such a combination maybe obtained with any of the body and marker configurations as definedabove.

Also, turning back to the marking device 100 in FIG. 1 A or the markingdevice 100 of FIG. 1 B, the markers 150 or 154 may be substituted withone or more suture or wire markers 158, preferably extending through thecenter and pointing radially away from the center. This configurationallows marking of the cavity perimeter and establishing of thedirectionality of the cavity itself.

Any of the previously-described additional features of the inventivedevice, such as presence of pain-killing or hemostatic drugs, thecapacity for the marker to emit therapeutic radiation for the treatmentof various cancers, the various materials that may make up the markerand body, and their size, shape, orientation, and geometry, may beincorporated into the device described above in conjunction with FIGS.3A-3D.

Turning now to FIGS. 4A-4C, a method of delivering the inventive deviceof FIG. 1A is shown. FIG. 4A details the marking device 402 just priorto delivery into a tissue cavity 404 of human or other mammalian tissue,preferably breast tissue 406. As can be seen, the step illustrated inFIG. 4A shows a suitable tubular percutaneous access device 400, such asa catheter or delivery tube, with a distal end 408 disposed in theinterior of cavity 404. As previously described, the marking device 402may be delivered percutaneously through the same access device 400 usedto perform the biopsy in which tissue was removed from cavity 404.Although this is not necessary, it is less traumatic to the patient andallows more precise placement of the marking device 402 before fluidbegins to fill the cavity 400.

FIG. 4B shows marking device 402 being pushed out of the distal end 408of access device 400 by a pusher 412 and resiliently expanding tosubstantially fill the tissue cavity 404.

Finally, in FIG. 4C, access device 400 is withdrawn from the breasttissue, leaving marking device 402 deployed to substantially fill theentire cavity 404 with radiopaque or echogenic marker 410 suspended inthe geometric center of the marking device 402 and the cavity 404. Asmentioned above, the marking device 402 may be sized to be larger thanthe cavity 404 thus providing a significant resistance against the wallsof the cavity 404.

FIGS. 4D-4F show a method of delivering the marking device 402 into atissue cavity 404 by a plunger 414 that is capable of both advancing themarking device 402 and delivering a biocompatible fluid 416. The“biocompatible fluid” is a liquid, solution, or suspension that maycontain inorganic or organic material. The fluid 416 is preferably asaline solution, but may be water or contain adjuvants such asmedications to prevent infection, reduce pain, or the like.Alternatively or additionally, the fluid may be used to mark thesentinel lymph node. Obviously, the fluid 416 is intended to be a typethat does no harm to the body.

FIG. 4D details the marking device 402 prior to delivery into the tissuecavity 404. In FIG. 4E, a plunger 414 pushes the marking device 402 outof the access device 400. Upon exiting the access device 400 the markingdevice 402 begins resiliently expanding to substantially fill the cavity404.

FIG. 4F shows the plunger 414 delivering the biocompatible fluid 416into the cavity 404. The plunger 414 may be equipped with a Luer orother type fitting to attach a fluid reservoir or syringe (not shown).The fluid 416 aids the marking device 402 in expanding to substantiallyfill the cavity 404. In this example, the biocompatible fluid 416 isdelivered subsequent to the placement of the marking device 402 in thecavity 404. The marking device 402 may also be soaked with fluid 416prior to placement in the cavity 404. Furthermore, the fluid 416 may bedelivered prior to delivery of the marking device 402.

FIGS. 4G-4I show another method of delivering the marking device 402into the tissue cavity 404 by using the biocompatible fluid 416 as theforce to deliver the marking device 402 into the tissue cavity 404.

FIG. 4G details the marking device 402 prior to delivery into the tissuecavity 404. FIG. 4H illustrates flow of the biocompatible fluid 416 inthe access device 400, the fluid 416 flow then pushes the marking device402 out of the access device 400.

FIG. 4I shows the delivery device 400 continuing to deliver thebiocompatible fluid 416 into the cavity 404. The fluid 416 aids themarking device 402 in expanding to substantially fill the cavity 404. Inthis example, the biocompatible fluid 416 is delivered after theplacement of the marking device 402 in the cavity 404 although theinvention is not limited to the continued delivery of the fluid 416.

FIGS. 4J-4L show the method of delivering the body 418 of the cavitymarking device directly into the cavity 404 prior to the placement ofthe marker 410 in the device 402.

FIG. 4J shows the deposit of the body material 418 into the cavity 404.In this case the body material 418 may be a gel type material asdescribed above. FIG. 4K details the filling of the cavity 404 with thebody material 418. At this point, the delivery device (not shown in FIG.4K) may be withdrawn. FIG. 4L details the placement of the marker 410into the body material 418.

FIGS. 5A-5E show yet another version of the invention in which a marker,preferably consisting of a radiopaque or echogenic wire, is deployedalone into a tissue cavity without the use of any body. In this device,the marker can be made of a shape memory material, such as anickel-titanium alloy, which, when deployed into the biopsy cavity,assumes a predetermined configuration to substantially fill the cavity,mark the cavity location and margin, and indicate the orientation of themarker inside the cavity. The open design of these deployable markersallows tissue in-growth, that further stabilizes the markers.Furthermore, the periphery of the cavity is marked with a relativelysmall amount of implanted material.

In FIG. 5A, marker 500 is a three-dimensional sphere consisting of tworings 502 and 504 pivotally connected at ends 506 and 508 so to assume aspherical shape. Such a marker can be made of a shape memory metal sothat when it is placed in a deployment tube 510 shown in FIG. 5B, marker500 assumes a collapsed profile suitable for deployment through tube 510by pusher 512. Upon exiting into the tissue cavity (not shown), marker500 assumes the spherical shape of FIG. 5A to fill the cavity. Themarker 500 may also be shaped into any similar shape such as anellipsoidal shape.

Turning now to FIG. 5C, a marker 520 in the form of a wire cylinder isshown. Again, this device is structurally configured to assume thedepicted cylindrical configuration when deployed in the tissue cavity,but may be (as described above) “collapsed” into a deployment tube forpercutaneous delivery. This device is especially suitable for markingthe distal and proximal ends of the tissue cavity due to itsasymmetrical shape.

FIG. 5D shows a shape memory marker 530 in the form of a helical coildeployed into tissue cavity 532. Again, as seen in FIG. 5E, such amarker 530 may be deployed through delivery tube 510 by pusher 512 in asubstantially elongated, straightened form, only to substantially assumethe shape of the cavity 532 as shown in FIG. 5D. Any suitable deliverydevice or pusher 512 capable of deploying marker 530 into cavity 532 iswithin the scope of this invention.

Each of the markers shown in FIGS. 5A-5E is preferably a shape memorymaterial coated or supplemented with a radiopacity-enhancing material,such as gold, platinum, or any other radiopaque material hereindiscussed. The markers may singly, or in combination with beingradiopaque, be echogenic or be made echogenic by any of the materials ormethods herein described.

Each of the markers shown in FIGS. 5A-5E is preferably self-centering.It is within the scope of the invention to add one or more materialssuch as a biocompatible liquid, gel, powder, or the like into the cavitybefore, during, or after delivery of those markers; the material mayprovide treatments such as hemostasis, antibiotic properties, or painrelief. In addition, a marker of any of the type shown in FIGS. 2A-2Gmay be inserted into the optional material to mark the center or providepatient information as described with respect to FIG. 2F.

FIGS. 6A-6D show a method of delivering the marking device 602 into atissue cavity 604 that allows the marking device 602 to radially expandto substantially fill the cavity 604 without the need for simultaneouspushing of the marking device 602 into the cavity 604. While the markingdevice 602 depicted in FIGS. 6A-6D is depicted as a bioabsorbablesurgical material with a marker placed at the geometric center of thedevice, the method is not limited to such devices. Any of the markerdevices described herein may be used with this method.

FIG. 6A details insertion of a sheath 600 into communication with tissuecavity 604. Preferably, the sheath 600 is placed through the same accesspathway (not shown) used by the biopsy device (not shown). The sheath600 is placed soon after the cavity 604 is formed.

FIG. 6B illustrates insertion of a cartridge or applicator 606 throughthe sheath 600 and into the cavity 604. The cartridge 606 may contain amarking device 602 and a disengaging arm (not shown.) Preferably, thecartridge 606 is advanced into the cavity 604 until the marking device602 is located within the cavity 604.

FIG. 6C illustrates the withdrawal of the cartridge 606 from the cavity604 and the partial expansion of the cavity marking device 602. As shownin the figure, the disengaging arm 608 within the cartridge 606 permitswithdrawal of the cartridge 606 independently of the marking device 602.Thus, the marking device 602 remains within the cavity 604. The use ofthe disengaging arm 608 permits the placement of the marking device 602while allowing for a significant frictional fit between the markingdevice 602 and the cartridge 606. This frictional fit minimizes thepossibility of accidental deployment of the marking device 602.

FIG. 6D illustrates the withdrawal of the cartridge 606 and thedisengaging arm 608 from the cavity 604 leaving the marking device 602to radially expand into the cavity 604. Although it is not shown, afterthe marking device 602 is placed within the cavity 604, fluid (notshown) may be delivered to the cavity 604 to assist the expansion of themarking device 602. Ultimately, the sheath 600 and cartridge 606 arewithdrawn from the cavity 604 and further withdrawn from the body.

FIGS. 7A-7K show devices for delivering a marking device into a tissuecavity which allow the marking device to radially expand tosubstantially fill the cavity without the need for simultaneous pushingof the marking device into the cavity.

FIG. 7A illustrates a variation of a disengagement arm 700 having distal704 and proximal 702 ends. The disengagement arm 700 of this figure hasfirst and second slots 706 and 708 that allow for a cartridge 710 andsheath 716 to have fixable positions along the disengagement arm 700.Although it is not shown, the disengagement arm 700 may be configured tohave a lumen (not shown) to provide delivery of fluid to the cavity toassist with the expansion of the marking device (not shown).

FIG. 7B illustrates a variation of a cartridge 710 having a lumen 712for placement of a marking device (not shown). The cartridge 710 has anoffset member 714 visible in FIG. 7C. In this embodiment, the offsetmember 714 engages with the first slot 706 of the disengagement arm 700to define a fixable position of the cartridge 710 along thedisengagement arm 700. FIG. 7D illustrates a sheath 716 having an offsetmember 718, as shown in FIG. 7E, which engages with the second slot 708of the disengagement arm 700 to define a fixable position of the sheath716 along the disengagement arm 700. The cartridge 710 may be rotatedabout the disengagement arm 700 so that the offset member 714 is removedfrom the slot 706 allowing the cartridge 710 to be moved to the proximalend of the disengagement arm 700.

FIG. 7F shows another variation of a disengagement arm 720 having distal724 and proximal 722 ends. The disengagement arm 720 of this variationhas a stop 726 that allow for a cartridge 730 and sheath 736 to havefixable positions along the disengagement arm 720. FIG. 7G shows avariation of a cartridge 730 having a lumen 732 for placement of amarking device (not shown). The cartridge 730 has a flange 734, as shownin FIG. 7H, which rests against the stop 726 of the disengagement arm720 to provide the cartridge 730 with a fixable position along thedisengagement arm 720. The cartridge 730 may be rotated about thedisengagement arm 720 so that an opening 738 in the flange 734 allowsthe cartridge 730 to be moved to the proximal end of the disengagementarm 722. On the cartridge 730 of FIG. 7G, a sheath may have a fixableposition along the cartridge 730 as the sheath is placed against aproximal end 742 of the cartridge 730. FIG. 71 shows a variation of thesheath 736 for use with the disengagement arm 720 and cartridge 730 ofFIGS. 7F and 7G. Although it is not shown, the disengagement arm 720 maybe configured to have a lumen (not shown) to provide delivery of fluidto the cavity to assist with the expansion of the marking device (notshown).

FIG. 7J illustrates the variations of the cartridge devices against aproximal end of the disengagement arms 720 and 700. FIG. 7K illustratesthe variations of the cartridge devices in a fixable position along thedisengagement arms 720 and 700. In these positions, the end portions 748and 740 of the cartridges 720 and 700 extend beyond the distal ends 724and 704 of the disengagement arms.

FIGS. 8A-8I illustrate a delivery device 800 and a method for using itto deliver a marking device 860 to a tissue cavity 874 accessed and/ormade by the probe 882 of a medical instrument 880. The probe 882 ispreferably between 1 and 25 mm in its largest cross sectional dimension(diameter, if circular), and most preferably between 2 and 5 mm.Although the marking device 860 is shown as the type shown in FIG. 1 K,it is not limited to such, and may be of any type disclosed in thisapplication or any other type.

As seen in FIG. 8A, the delivery device 800 includes an outer sheath 810having a proximal entryway 812 for the probe 882 (shown in FIG. 8B). Theouter sheath 810 further includes an outer sheath hub 814 and anoptional side port 816. The outer sheath 810 may be circular ornoncircular in cross section regardless of whether the probe 882 has acircular or noncircular cross section. For example, if the outer sheath810 is flexible and circular in cross section, but the probe 882 isshaped like a “figure 8”, the outer sheath 810 may conform to follow thecontours of the probe when the outer sheath is placed over the probe.For example, for a probe having such a figure 8 configuration with itslargest cross sectional dimension about 4.6 mm and its smallest about 3mm; the outer sheath may have a circular cross section with an innerdiameter of about 4 mm. The delivery device 800 further includes anapplicator 820, which is made up of an inner sheath 830 and a plunger840. The inner sheath 830 may further comprise an inner sheath hub 832,a safety lock 834 with a safety tab 835, a stop 836, and a distalportion 838 that is distal of the stop 836. A marking device 860 may bepreloaded within the distal portion 838 of the inner sheath 830. For theexample above of a 4-mm inner diameter outer sheath, the inner sheathwill easily accommodate a marking device having a compressed diameter upto about 3.3 mm. The inner sheath hub 832 is preferably immovable on theinner sheath 830, providing both a grip for pushing the plunger 840 anda support for the safety lock 834. Furthermore, the inner sheath hub 832may also function as a stop, thereby eliminating the need for separatestop 836. The distal portion 838 of the inner sheath 830 is sized to fitthrough either the entryway 812 or the side port 816 of the outer sheath810 up to the inner sheath stop 836. The delivery device 800 preferablyincludes a guide 850 having a clamp 852 for attachment to a first pointthat is fixed with respect to a desired marking site within the patient.This first fixed point could be, for example, on the patient herself, ona stereotactic table, or on an attachment on a stereotactic table, suchas a rail, a fixed portion of a driver attached to the stereotactictable, or the like. The guide 850 has a channel 854 through which theouter sheath 810 may slide. The guide 850 also has a locking mechanism856 that can engage the outer sheath hub 814. The inner and outersheaths are preferably made of Pebax, a fluoropolymer such as Teflon O,or polyethylene, and may be radiopaque or echogenic. The hubs 814 and832 and guide 850 are preferably made of polycarbonate or polypropylene.

As shown in FIG. 8B, to use the delivery device 800, the outer sheath810 is placed over a probe 882 of a medical instrument 880, such as abiopsy probe.

As shown in FIG. 8C, a guide 850 preferably is attached, using a clamp852, to a first point 858 that is fixed with respect to the patient 870,such as a fixed point on the medical instrument 880, a rail of astereotactic table 890 (as shown), or the patient herself. The probe 882with the outer sheath 810 is introduced through the channel 854 of theguide 850, through the skin 872 of the patient 870, and into the sitewhere the marker is to be deployed; this step may comprise taking atissue sample, thus creating a cavity 874 in the tissue.

As shown in FIG. 8D, while the probe 882 and outer sheath 810 are heldstationary with respect to the patient 870, the guide 850 is moved fromthe first fixed point 858, then slid along the outer sheath 810 towardthe outer sheath hub 814 to a second fixed point 859 along the rail ofthe stereotactic table 890. (Alternatively, the second fixed point 859may be a point on the medical instrument 880 or the patient 870 or otherconvenient place to keep the outer sheath 810 stationary with respect tothe patient 870 during delivery of the marking device.) The guide 850 isconnected to the outer sheath hub 814, such as with a friction or snapfit of the locking mechanism 856.

As shown in FIG. 8E, the medical instrument 880 is then at least partlyretracted from both the patient 870 and the stationary outer sheath 810,leaving the outer sheath 810 in communication with the biopsy cavity874. If a side port 816 is used, as shown, the probe 882 may beretracted just far enough to allow access to the cavity through the sideport 816; the distal end of the probe 882, which is typically sharp, mayremain protected by the proximal end of the outer sheath 810, and is notrequired to be retracted past the outer sheath entryway 812. However, ifa side port 816 is not provided on the outer sheath 810 or is otherwisenot used, the probe 882 must be fully retracted to clear the entryway812. Furthermore, for side port access, the outer sheath 810 may berotated within the guide 850 to ensure that side port 816 is oriented tobe accessible to the operator.

As shown in FIG. 8F, an applicator 820 comprising an inner sheath 830and a plunger 840 preferably is inserted into a side port 816 of theouter sheath 810 until the stop 836 is reached and the distal end 831 ofthe inner sheath 830 protrudes through the distal end 818 of the outersheath 810. The inner sheath 830 is preferably flexible to bend toaccess the side port 816. Alternatively, it may be preshaped in a bendor curve to access the side port 816. Furthermore, plunger 840 isflexible to access side port 816; it, too, may have a preshaped curve.Alternatively, the probe 882 may be retracted clear of the proximalentryway 812, and the applicator 820 may be inserted through theproximal entryway 812.

FIGS. 8G-8I illustrate deploying the marking device 860. As shown by thearrow in FIG. 8G, a safety lock 834 is unlocked by depressing a safetytab 835 on the applicator 820 to release the plunger 840. The plunger840 is pushed into the inner sheath 830, as shown by the arrow in FIG.8H, to deploy the preloaded marking device 860 into the tissue cavity874, as shown in FIG. 8I. Although not shown, a Luer or other typefitting may be provided on the delivery device for fluid infusion. Thedelivery device 800 is removed from the patient 870.

The delivery device of FIGS. 8A-8I may be used to deliver a markingdevice to a surgically-created cavity by introducing the distal end ofthe outer sheath through the surgical incision and into the cavity.

FIGS. 9A-9F illustrate a delivery device 900 and a method for using itto deliver a marking device 960 to a tissue cavity 974 laterally througha side window 986 of a cannula 982 of a medical instrument 980. (SeeFIG. 9D.) Although the marking device 960 is shown as the type shown inFIG. 1 K, it is not limited to such, and may be of any type disclosed inthis application or any other type known in the art. It is preferablyimplantable without needing to be removed. The medical instrument 980may be a biopsy device as described above, or may be any other medicalinstrument having a cannula 982 with an entryway 988 through which thedelivery device 900 can enter, a stop 984 that can limit travel of thedelivery device 900, and a side window 986 proximate the distal end 985through which the marking device 960 can be deployed. The probe 982 ispreferably between 1 and 25 mm in its largest cross sectional thickness(diameter, if circular), and most preferably has an inner diameter of2.5 to 4 mm. The stop 984 may completely or only partially block thedistal end 985 of the cannula 982 or may be located elsewhere to limittravel of the delivery device 900.

As shown in FIGS. 9A-9B and by way of example, the delivery device 900preferably includes a shaft 920, which has a flexible shaft portion 930,a proximal handle portion 932, a rotational position indicator 934, anda cutout 936 in the proximal handle portion 932 for mating with afeature 989 of the medical instrument 980 (shown in FIG. 9C). Thisfeature 989 may be the tip of a slidable rod that aids in ejecting atissue sample from the medical instrument 980, which in this case isshown as a biopsy instrument. As shown in FIGS. 9D-9F, the flexibleshaft portion 930 is flexible enough in bending to allow it to beintroduced through the entryway 988 of the cannula 982 of the medicalinstrument 980, yet stiff enough in compression to allow it to be pushedthrough the cannula 982. Distal of the flexible shaft portion 930 is adistal shaft portion 938, comprising an ejector 940 having a seat 942 onwhich the preloaded marking device 960 (shown in FIG. 9D) rests prior todelivery and from which the marking device 960 is ejected laterallythrough the side window 986 of the cannula 982 (shown in FIG. 9F). Theejector 940 further comprises one or more living hinges 944. The entireshaft 920 except for the proximal handle portion 932 is s size and shapeto provide an interference fit between the marking device 960 and theseat 942.

As shown in FIG. 9E, the distal end of the shaft 920 is placed throughthe cannula entryway 988 and aligned so that the marking device 960 isin line with the side window 986. The rotational position indicator 934in proximal handle portion 932 aids in determining the orientation ofthe marking device 960. In the case where the retainer 910 is a tube,block, clip, or the like, the retainer 910 may be transient as shown,sliding toward the proximal end of the shaft 920 as the delivery device900 enters the cannula 982. The marking device 960 remains capturedbetween the seat 942 and the cannula 982 as the shaft 920 with markingdevice 960 is slid through the cannula 982. This differs from some ofthe prior art clipping devices that are carried on a wire that must becut when the clip reaches its intended location.

As shown in FIG. 9F, using the proximal handle portion 932, the shaft920 is advanced so that the distal end of the shaft 920 contacts thecannula stop 984. Advancement of the shaft 920 continues until theejector 940 ejects the marking device 960 from the seat 942, through thecannula side window 986, and into the tissue cavity 974. As shown here,the ejection step may occur by buckling the shaft 920 in the region ofthe ejector 940, pushing the seat 942 toward the cannula side window986. This may be facilitated by using one or more living hinges 944. Acutout 936 in the proximal handle portion 932 may be mated with a matingfeature 989 in the medical instrument 980 to indicate that the shaft 920is in the correct position such that the ejector 940 has ejected themarking device 960. Preferably, the ejector 940 remains completelywithin the cannula 982 without any portion of it passing through theside window 986. This helps to ensure that the marking device 960 isdelivered directly out of the side window 986 without pushing it to someunknown location further away. The retainer 910 may comprise a tubehaving a slit 912 or other means of expanding its proximal end to fitover the proximal handle portion 932. The retainer 910 preferablyremains captured on the shaft 920 between the proximal handle portion932 and the cannula entryway 988. Although not shown, after the markingdevice 960 has been ejected through the side window 986, the cannula 982preferably is rotated about 180 so that the side window 986 is away fromthe deployed marking device 960. The medical instrument 980 and deliverydevice 900 are then retracted from the patient 980. Preferably, theejector 940 is designed to substantially cover the window 986 of themedical instrument 980 to prevent drag on and/or injury to tissue or themarking device on the way out.

FIGS. 10A-10H illustrate an alternative delivery device 1000 and methodfor using it to deliver a marking device 1060 to a tissue cavity 1074laterally through the side window 1086 of a cannula 1082 of a medicalinstrument 1080. The delivery device 1000 is similar to that of deliverydevice 900 in that its main features are (1) an ejector seat for holdingand ejecting a marking device laterally through a side window whileremaining within the cannula and (2) a flexible shaft for pushing theejector seat and marking device through the cannula. The medicalinstrument 1080 may be a biopsy device as described above, or may be anydevice having a cannula 1082 with an entryway 1088 through which thedelivery device 1000 can enter, and a side window 1086 proximate thedistal end 1085 through which the marking device 1060 can be deployed.The cannula 1082, and therefore the portion of the delivery devicesliding through cannula 1082, is preferably between 1 and 25 mm in itslargest cross sectional thickness (diameter, if circular), and mostpreferably has an inner diameter of 1.5 to 4.5 mm. In a preferredembodiment, cannula 1082 has an inner diameter of about 2.7 mm, allowingdelivery of a marking device 1060 having a compressed diameter of about2.5 mm. Although the marking device 1060 is shown as the type shown inFIG. 1 L, it is not limited to such, and may be of any type disclosed inthis application or any other type known in the art. The marking device1060 is preferably one that can be simply released into the marking sitewithout requiring clipping or piercing tissue.

As shown in FIG. 10A, the delivery device 1000 includes an applicator1020, which has a sheath 1030 and a plunger 1040. A portion of sheath1030 and a portion of plunger 1040 together form a flexible shaftportion 1022, which can bend to fit through entryway 1088 and is rigidenough to push the ejector seat with its marking device through thecannula 1082. The sheath 1030 further comprises a proximal handleportion 1032 and a collapsible sleeve 1031 at or near its distal end. Asshown in FIG. 10B, sleeve 1031 forms an ejector seat 1033, preferablyU-shaped, in its collapsed condition on which the preloaded markingdevice 1060 rests prior to delivery and from which the marking device1060 is ejected through the side window 1086 of the cannula 1082 (shownin FIG. 10C). The sleeve 1031 is preferably made of a high yieldstrength plastic such as PET, polyimide, polycarbonate, or acrylic, andis preferably of a size and shape that the material does not have toyield when expanding to eject the marking device 1060. The sleeve 1031and distal portion of the sheath 1030 are sized to fit through thecannula 1082 of the medical instrument 1080 (shown in FIG. 10C). Thesheath 1030 further comprises a clip 1035 that is preferably immovableon the sheath 1030, and includes one or more features 1036, such as anotch, indentation, recess or hole, to mate with a feature 1089 on themedical instrument 1080 (shown in FIG. 10C). The sheath 1030 ispreferably made of Pebax, a fluoropolymer such as Teflont), orpolyethylene, and is preferably radiopaque and/or echogenic. The clip1035 is preferably made of polycarbonate or polypropylene. The plunger1040 further comprises a proximal handle portion 1042 and a piston 1045and is capable of expanding the sleeve 1031 by filling it with anexpander 1044, which may be a fluid, such as saline or air, orpreferably a solid, such as the distal portion of the piston 1045 asshown. In the case where the expander 1044 is a fluid, the sleeve 1031may be sealed to form a balloon that keeps the fluid within the deliverydevice. Alternatively, the sleeve 1031 may have one or more openings(not shown) to allow the fluid to not only expand the sleeve 1031 but tobe delivered to the body; this is useful for delivering fluids havinghemostatic, pain-reducing, antibiotic, sentinel node-detecting, and/orbody expanding properties; the body expanding properties may work byhydrating or by chemically reacting with the body material. To injectthe fluid through the plunger 1040, whether the sleeve 1031 is open orclosed, the plunger 1040 may further include a Luer or other typefitting for connection to a fluid reservoir or syringe (not shown).Additionally or alternatively, fluids may be infused through a vacuumsystem on the medical instrument. In the case where the expander 1044 isa solid, the sleeve 1031 may be open or closed.

As shown in FIG. 10C, to use the delivery device 1000, the cannula 1082of the medical instrument 1080 is introduced into the site where themarking device 1060 is to be deployed; as described before, this stepmay comprise taking a tissue sample, thus creating a cavity 1074 in thetissue. The side window 1086 and lumen of the cannula 1082 arepreferably cleared of tissue debris, such as by applying a vacuum;additionally, the cannula may be flushed with saline, which is thenaspirated. The applicator 1020 is preloaded with a marking device 1060,which sits in the ejector seat 1033 formed in the collapsed sleeve 1031.It is held in place by a retainer 1010, which may be a tube (as shown),a block, a clip, or the like, of a size that will not pass through thecannula 1082.

As shown in FIG. 10D, the distal end of the applicator 1020 is placedthrough the cannula entryway 1088 and aligned so that the marking device1060 is in line with the side window 1086. This alignment can beachieved by ensuring that the side window 1086 is in its “12 o'clock”rotational position, as shown, and orienting the marking device 1060 sothat it is facing the same direction as the side window 1086 and so thatthe clip 1035 with its mating feature(s) 1036 will match up with thefeature 1089 on the medical instrument 1080. Because the retainer 1010cannot pass through the cannula 1082, it is a transient retainer anddoes not remain in place to hold the marking device 1060 in seat 1033;as the delivery device 1000 enters the cannula 1082, the retainer 1010is slid off the marking device 1060 and remains outside the cannula1082. The marking device 1060 remains captured between the seat 1033 andthe cannula 1082 as the applicator 1020 with its marking device 1060 isslid through the cannula 1082.

As shown in FIGS. 10E-10H, the applicator 1020 is advanced until theclip 1035 on the sheath 1030 abuts the proximal end of the retainer1010, thus capturing the retainer 1010 between the clip 1035 and thecannula entryway 1088. The clip 1035 is then clipped onto the medicalinstrument 1080 by mating the clip and medical instrument features, 1036and 1089. The plunger 1040 is then pushed until the expander 1044expands the sleeve 1031, ejecting the marking device 1060 from the seat1033, through the cannula side window 1086, and into the tissue cavity1074. Preferably, all parts of the applicator 1020 that enter thecannula 1082 remain completely within the cannula 1082 without anyportion passing through the side window 1086. This helps to ensure thatthe marking device 1060 is delivered directly out of the side window1086 without pushing it to some unknown location further away. As shownin FIG. 10G-10H, after the marking device 1060 has been ejected throughthe side window 1086, the cannula 1082 is preferably rotated about 180so that the side window 1086 is away from the deployed marking device1060. This guarantees that only a smooth, non-cutting side of thecannula faces the marking device 1060 during withdrawal of the medicalinstrument 1080 to avoid dislodging the marking device 1060.Furthermore, an advantage of this system is that once the sleeve isexpanded it substantially covers the side window thus protecting thetissue. In fact, prior art through cannula clip delivery devicestypically require extra steps of withdrawing the clip applier andreinserting an inner cannula to protect the tissue from the sharp windowand to avoid dislodging the clip. The medical instrument 1080 anddelivery device 1000 are then retracted from the patient 1070.

FIGS. 11A-11E illustrate an alternative delivery device 1100 and methodfor using it to deliver a marking device 1160 to a tissue cavity 1174laterally through the side window 1186 of a cannula 1182 of a medicalinstrument 1180. The medical instrument 1180 is preferably a biopsydevice as described above, or may be any device having a cannula 1182with an entryway 1188 through which the delivery device 1100 can enter,and a side window 1186 proximate the distal end 1185 through which themarking device 1160 can be deployed. Although the marking device 1160 ispreferably the type shown in FIG. 1L, it is not limited to such, and maybe of any type disclosed in this application or any other known in theart. Marking device 1160 is preferably implantable and can be left inthe body indefinitely.

As shown in FIG. 11A, the delivery device 1100 includes an applicator1120, which has a sheath 1130 and a plunger 1140. A portion of thesheath 1130 and a portion of the plunger 1140 together form a form aflexible shaft portion 1122, which can bend to fit through entryway 1188and is rigid enough to push the ejector seat with its marking devicethrough the cannula 1182. The sheath 1130 further comprises a proximalhandle portion 1132 and a collapsible sleeve 1131 that forms an ejectorseat 1133 in its collapsed condition (similar to seat 1033 shown in FIG.10B) on which the preloaded marking device 1160 (shown in FIG. 11 C)rests prior to delivery and from which the marking device 1160 isejected through the side window 1186 of the cannula 1182. The sleeve1131 is preferably made of a high yield strength plastic such as PET,polyimide, polycarbonate, or acrylic, and is preferably of a size andshape that the material does not have to yield when expanding to ejectthe marking device 1160. The sheath 1130 further comprises a clip 1135that is immovable thereon, having a clip feature 1136. The plunger 1140further comprises a proximal handle portion 1142 and a piston 1145 andis capable of expanding the sleeve 1131 by filling it with an expander1144, which may be a fluid, such as saline or air, or preferably asolid, such as the distal end of piston 1145 as shown. In the case wherethe expander 1144 is a fluid, the sleeve 1131 is sealed to form aballoon. Alternatively, the sleeve 1131 may have one or more openings(not shown) to allow the fluid to not only expand the sleeve 1131 but tobe delivered to the body; this is useful for delivering fluids havinghemostatic, pain-reducing, antibiotic, sentinel node-detecting, and/orbody expanding properties; the body expanding properties may work byhydrating or by chemically reacting with the body material. In the casewhere the expander 1144 is a solid, the sleeve 1131 may be open-orclosed-ended. A separate fitting may be provided on the sheath 1130 fordrug or saline infusion through the sheath 1130. The distal end of theapplicator 1020 is sized to fit through the cannula 1182 of the medicalinstrument 1180 (shown in FIG. 11 C). The delivery device 1100 furtherincludes a retainer 1110 having a key on its distal end for locking intoa keyway 1183 in the cannula 1182 (shown in FIG. 11B). The retainer 1110further includes a hub 1114 at or near its proximal end with a feature1115 for connecting to the clip feature 1136 on the sheath clip 1135.

As shown in FIG. 11 C, to use the delivery device 1100, the cannula 1182of the medical instrument 1180 is introduced into the site where themarking device 1160 is to be deployed; as described before, this stepmay comprise taking a tissue sample, thus creating a cavity 1174 in thetissue. The side window 1186 and lumen of the cannula 1182 arepreferably cleared of tissue debris, such as by applying a vacuum;additionally, the cannula may be flushed with saline, which is thenaspirated. The applicator 1120 is preloaded with a marking device 1160,which sits in the seat 1133 (see seat 1033 in FIG. 10B) formed in thecollapsed sleeve 1131. It is held in place by the retainer 1110, whichmay be a tube (as shown), a block, a clip, or the like. As will be seenlater, it is not necessary that the side window 1186 of the cannula 1182be in its “12 o'clock” position to align the marking device 1160 withthe side window 1186. The keyway 1183 rotates with the cannula 1182, andtherefore is in line with the side window 1186.

As shown in FIG. 11 D, the distal end of the applicator 1120 andretainer 1110 are placed through the cannula entryway 1188 and alignedso that the retainer key 1112 enters keyway 1183 of the cannula 1182. Asthe delivery device 1100 enters the cannula 1182, the retainer 1110 isslid off the marking device 1160. The applicator 1020 is pushed forward,aligning the feature 1136 in the sheath clip 1135 with the feature 1115in the retainer hub 1114 and connecting them together, thus capturingthe retainer 1110 between the cannula entryway 1188 and the sheath clip1135. By locking the sheath clip 1135 to the retainer hub 1114, andbecause the retainer 1110 is locked into the keyway 1183 and istherefore rotationally fixed with respect to the cannula 1182, themarking device 1160 will always face the direction that the side window1186 is facing. Therefore, the marking device 1160 may be delivered whenthe medical instrument 1180 has its cannula 1182 and side window 1186 inany clock position, and is not limited to delivering in only the 12o'clock position. The marking device 1160 remains captured between theseat 1133 and the cannula 1182 as the applicator 1120 with its markingdevice 1160 is slid through the cannula 1182.

As shown in FIG. 11E, the safety lock 1134 on the proximal handleportion 1132 is then unlocked, and the plunger 1140 is pushed until theexpander 1144 expands the sleeve 1131, ejecting the marking device 1160from the seat 1133, through the cannula side window 1186, and into thetissue cavity 1174. Preferably, all parts of the applicator 1120 thatenter the cannula 1182 remain completely within the cannula 1182 withoutany portion passing through the side window 1186. This helps to ensurethat the marking device 1160 is delivered directly out of the sidewindow 1186 without pushing it to some unknown location further away.After the marking device 1160 has been ejected through the side window1186, the cannula 1182 is rotated about 180 so that the side window 1186is away from the deployed marking device 1160. As with delivery device1000, an advantage of delivery device 1100 is that once the sleeve isexpanded it substantially covers the side window 1186 thus protectingthe tissue. The medical instrument 1180 and delivery device 1100 arethen retracted from the patient 1170.

As can be seen from the embodiments of FIGS. 9A-9F, 10A-10G, and11A-11E, delivery of a marking device into a cavity through a windowprovides several advantages. As examples, the track created is only aslarge as the cannula used to create the cavity, the number of steps inthe procedure is reduced because the site is positively located by thecannula itself and does not have to be relocated, and the marking devicewill be delivered to the correct location.

From the foregoing, it is understood that the invention provides animproved subcutaneous cavity marking device and method. While the abovedescriptions have described the invention for use in the marking ofbiopsy cavities, the invention is not limited to such. One suchapplication is evident as the invention may further be used as alumpectomy site marker. In this use, the cavity marking device yields animproved benefit by marking the perimeter of the lumpectomy cavity.Other such applications of the invention include delivering a marker toa naturally occurring body cavity and delivering a marker to an area oftissue that does not have a cavity. Furthermore, although some of theembodiments described herein were described with respect to apercutaneous procedure, they may be used in an open surgical procedureas well; in that case, the marking device may be delivered by handwithout the use of a delivery system, and the marking device may notrequire compression for delivery through a small opening. Also, themarking system may be provided as a kit, wherein the marking device ispreloaded in the delivery device; alternatively, the marking device maybe provided separately for loading into the delivery device by theoperator, with or without the aid of a loading tool, which also may beprovided in the kit. The kit may be provided with variously sized and/orvariously shaped marking devices, allowing the operator to choose theparticular device most suited for the cavity to be marked. Having morethan one marking device available in the kit also allows the operator tomark more than one location, if needed.

Furthermore, as will be described with respect to FIGS. 12A-12C and13A-13B, the present invention provides an alternative composition andmethod to remotely detect sentinel lymph nodes to determine whethercancerous cells have spread thereto. This method includes thedeposition, preferably by one of the delivery devices described hereinor by injection via a thin needle applicator, of a remotely detectablecontrast agent that migrates to the SN. Upon accumulating in the SN, theremotely detectable contrast agent allows a physician to pinpoint thelocation of the SN to target the SN for removal using minimally invasivetechniques. The composition is preferably capable of migrating frombreast tissue to a lymph node in a predetermined amount of time.Preferably, less than 3 hours, and more preferably within 5 to 20minutes. To migrate within this timeframe, the contrast agent preferablycomprises particles between 0.05 microns and 5 microns in diameter. Thecomposition and method eliminates the need for potentially toxicradioactive tracer material. In addition, the lack of toxicity of suchagents obviates the need to remove the lesion and/or the SN on the sameday. The contrast agent is preferably either permanently implantable orshort-lived, never requiring removal.

These agents may be any biologically compatible agents capable of remotedetection. Examples of such remote detection include, but are notlimited to, magnetism such as a magnetometer, Hall effect sensor, ormagnetic resonance imaging (MRI); ultrasound; X ray, fluoroscopy, or CT;thermal means; high intensity ultraviolet techniques; fluorescent dyetechniques; etc.; singly or in combination.

One example of such a contrast agent is an echogenic microsphere capableof reflecting ultrasonic energy. These microspheres, preferablyaveraging typically between 0.2 microns and 5 microns in diameter, andpreferably less than 2 microns in diameter, may be mixed with abiologically compatible carrier fluid and injected into the body in thevicinity of the lesion, where they will accumulate in the SN. Theechogenic microspheres may comprise hollow bubbles fill with air, CO2,nitrogen, or fluorinated gas. For example, these microbubbles maycomprise microencapsulated perfluorocarbon. The echogenic contrast agentmay, but does not necessarily, contain microparticles of silicon or asilicon compound, such as silicone or Si02, preferably in a dilutesuspension. Upon an exposure to ultrasonic energy, the spheres reflectthe energy creating an ultrasonic reflection. The ultrasonic-reflectionresulting from a large number of the microspheres that have accumulatedin the SN permits detection of the particular node by a conventionalultrasonic probe. Another example of an agent is a biologicallycompatible magnetically detectable body such as a magnetic microsphere.Such a magnetically detectable body can be the echogenic microspheredescribed above that is either fabricated from or coated with a magneticmaterial; alternatively, it may be a solid or other type of magneticbody capable of being incorporated into a carrier fluid and depositedaround the lesion or its cavity as described herein. These bodies shouldbe capable of migration to and accumulation in the SN so that, in asimilar fashion to the echogenic microspheres, the cumulative magneticfield presented by these magnetic bodies allows one to remotely andnoninvasively determine the location of the SN.

As an alternative or addition to being echogenic, the contrast agent mayhave sufficient radiopacity to be detectable using fluoroscopy,mammography, or other X ray imaging.

FIGS. 12A-12C show a method for locating the sentinel lymph node in amammalian body to determine if cancerous cells have spread thereto. Themethod includes (1) depositing a remotely detectable fluid in or arounda lesion for migration to and accumulation in the associated sentinelnode and (2) remotely detecting the location of that node with a minimumof trauma and toxicity to the patient. The composition used for locatingthe sentinel node is preferably a fluid composition consisting of acarrier fluid and some type of non-radioactive contrast agent asdescribed above. Alternatively, the contrast agent may also be a fluidand therefore not require a separate carrier fluid to migrate to thenode. This composition is capable of (1) deposition in or around alesion and migration to and accumulation in the associated sentinelnode, and (2) remote detection a noninvasive technique. The compositionmay additionally be capable of being directly visualized such as byadding blue dye to the noninvasively-detectable contrast agent toconfirm that the appropriate lymph node was removed. Carbon may be, butis not necessarily, added to the contrast agent for histologicalconfirmation.

FIG. 12A depicts the first steps of a method for locating a sentinelnode 1200 comprising injecting a noninvasively detectable,non-radioactive, migratory contrast agent 1210 into the region of acavity or lesion 1220, then waiting sufficient time for the contrastagent to migrate through the lymph ducts 1230 to at least one lymph node1200 in the axillary region 1250. In general, the smaller the particlesize of the contrast agent, the faster it will migrate; also, generallyless viscous compositions will migrate faster. Furthermore, the closerin the size the particles are to each other, the narrower the window oftime will be for most of the particles to reach the sentinel node. Theparticles may be filtered or otherwise selected to be very close insize; alternatively, they may vary widely; as another alternative, theymay have a bimodal size distribution with the smaller size for earlysentinel node detection and the larger size for accumulation throughoutthe lymph nodes, as will be described below. The contrast agent may beinjected directly into a biopsy or lumpectomy cavity; or it may beinjected intradermally or periareolarly (around the area of the areola1240), before, after, or without creation of a cavity. While waiting forthe contrast agent to migrate, massage and/or compression may beadministered to the patient to speed migration of the contrast. Also, abiopsy or lumpectomy may be performed during the waiting period, if notalready done (not shown). This latter order of steps may be preferred bysome who believe that creating the cavity may disturb the lymph ducts1230, slowing down or preventing migration of the contrast agent to thesentinel node.

As shown in FIG. 12B, the contrast agent 1210 is noninvasively detectedin at least one lymph node 1200. Examples of non-invasive detectionmethods include, but are not limited to using ultrasound, fluoroscopy,MRI, a Hall Effect sensor or magnetometer, or other imaging means. Inthe embodiment depicted in FIG. 12B, the contrast agent 1210 isechogenic, and an ultrasound probe 1260 is used to scan the axilla 1250while watching the ultrasound monitor 1270. Preferably, only one lymphnode is identified as containing contrast agent and, therefore, is the“sentinel node”; however, the contrast agent may accumulate in 2 or 3lymph nodes almost simultaneously, with up to 3 being considered“sentinel nodes”, as shown. Particularly for contrast agents having alow viscosity and a uniformly small size, such as an average of lessthan 0.05 microns and an upper limit of 0.1 microns. Given thisconfiguration, lymphatic system will quickly take up the contrast agent.The contrast agent will then quickly migrate to the sentinel node, thento the next node and so on. In that case, the physician must be carefulto not wait too long between injection and detection.

As shown in FIG. 12C, lymph tissue containing the contrast agent 1200 isthen either sampled, using fine needle aspiration (FNA) or core biopsy,or completely removed, percutaneously, endoscopically, laparoscopically,or using conventional surgery. A percutaneous tissue removal device 1280may be used, such as those described in U.S. Pat. Nos. 5,913,857 and5,810,806 and U.S. application Ser. Nos. 09/184,766 and 09/145,487 toVivant Medical, Inc. The tissue sampling or removal is preferably doneusing ultrasound, especially in the case where ultrasound is used todetect the contrast agent. The ultrasound probe 1260 held over thesentinel node 1200 that was detected in the axilla 1250 while the markedtissue is sampled. Alternatively or additionally, the tissue sampling orremoval may be done using fluoroscopy, especially in the case where thecontrast agent is radiographic. As another alternative, the tissuesampling or removal may be done using MRI. Many of the prior-artradioactive tracer methods required separate procedures for detectingthe sentinel node under the skin, marking the location on the skin witha dot, alternating between a gamma probe and an ultrasound probe to markthe SN with a wire, then surgically removing the SN and wire. However,in the present invention, it is desirable to use the same imagingmodality to detect the sentinel node and to sample or remove it.Following the sentinel lymph node sampling or removal, the patient maybe noninvasively checked to see whether all the contrast was removed.However, it is preferable that the contrast be completely implantable,not requiring removal. Furthermore, many of the commercially-availableechogenic contrast agents suitable for this method are short-lived, andtherefore do not require removal.

The removed tissue is evaluated histologically for cancer. If cancer isfound in the sentinel lymph node, the migrating and accumulatingproperties of the contrast agent can be used to determine whereadditional lymph nodes are that should be removed. That is, the contrastagent that was used to detect the SN can be one that accumulates quicklyin the first node (“sentinel node”) for identification within preferably5 to 20 minutes. The agent will continue to migrate through thelymphatic system, but preferably more slowly, with a portion of thecontrast agent accumulating in each lymph node for detecting during awindow of approximately 1 day to 1 month following injection. Thisfacilitates detection of additional lymph nodes that the physician maywant to remove in the case where cancer is detected in the sentinelnode. Removing such lymph nodes may be therapeutic by decreasing thetumor burden, thus increasing the efficacy of subsequent chemotherapy.The lymph nodes preferably are removed percutaneously using imageguidance of the same modality used to detect them.

FIGS. 13A-13B show a method for marking a biopsy or lumpectomy cavityand locating the sentinel lymph node that had served the tissue removedfrom the cavity to determine if cancerous cells have spread thereto. Thecomposition for locating the sentinel lymph node is preferably a fluidcomposition consisting of a carrier fluid and some type of contrastagent as described above; alternatively, the contrast agent may itselfbe a fluid and therefore not need a separate carrier fluid. Thiscomposition is capable of (1) deposition in or around a lesion andmigration to and accumulation in the associated sentinel node, and (2)detection, preferably by noninvasive means, and/or by directvisualization. Also disclosed is a method for marking a cavity anddetecting the location of a sentinel node by (1) depositing a markingdevice with a detectable composition in the cavity for migration to andaccumulation in the associated sentinel node and (2) detecting thelocation of that node with a minimum of trauma and toxicity to thepatient.

FIG. 13A depicts the first steps of a method for marking a biopsy orlumpectomy cavity 1315 in the breast 1313 and locating a sentinel node1300 in the axilla 1350, comprising inserting a subcutaneous markingdevice 1312 according to the present invention and using a deliverydevice 1305 according to the present invention. A contrast agent 1310 isincluded in the marking device 1312, either as the body of the markingdevice (as shown), which may degrade, allowing detectable microparticlesto migrate to the lymph nodes. Alternatively, the contrast agent 1310 asa separate composition that is added to the marking device, before,during, or after its insertion into the cavity (e. g., see FIGS. 4D-4I,1 OA-1 OH, and 1 lA-l lE). Following marking device/contrast agentinsertion, while waiting for the contrast agent to migrate to a lymphnode, massage and/or compression may be administered to the patient tospeed migration of the contrast.

In a similar manner as depicted in FIG. 12B, the contrast agent isnoninvasively detected in at least one lymph node. Examples of suchnon-invasive methods includes, but are not limited to, ultrasound,fluoroscopy, MRI, or a Hall Effect sensor or magnetometer, or otherimaging. The imaging used to detect the contrast agent may be, but isnot necessarily, the same as that used to detect the cavity markingdevice.

As shown in FIG. 13B, lymph tissue containing the contrast agent is theneither sampled, using fine needle aspiration (FNA) (shown here) or corebiopsy, or completely removed, endoscopically, laparoscopically, orusing conventional surgery. As shown in this example, marking device1312 has expanded to fill cavity 1315. Some of the contrast agent 1310has migrated away from the marking device 1312 and has accumulated inthe sentinel node 1300, where an ultrasound probe 1360 is used to guidea needle 1390 for fine needle aspiration. As described above, the tissuesampling or removal may be done using ultrasound, fluoroscopy, MRI, orany other suitable imaging technique. Alternatively, the contrast agentmay be visible under direct visualization, and the tissue may besurgically removed without any image guidance. As another alternative,the contrast agent may be a radioactive tracer, and a gamma probe and/orlymphoscintigraphy may be used in combination with ultrasound, asdescribed above, to detect and remove the sentinel node. A percutaneoustissue removal device may be used, such as those described in PCTpublication WO 99/25248; U.S. Pat. Nos. 5,913,857 and 5,810,806; andU.S. application Ser. Nos. 09/184,766 and 09/145,487 to Vivant Medical,Inc.

Once removed, the tissue sample is evaluated for the presence of cancer.If cancer is found in the sentinel lymph node, the contrast agent canagain be used to determine where additional lymph nodes are that shouldbe removed. As described above, a contrast agent can be used that willaccumulate quickly in the first node (“sentinel node”) foridentification within preferably 5 to 20 minutes. The agent willcontinue to migrate through the lymphatic system, but more slowly, witha portion of the contrast agent accumulating in each lymph node fordetecting during a window of approximately 1 day to 1 month followinginjection. This provides an easy way to detect the additional lymphnodes that may need to be removed in the case where cancer is detectedin the sentinel node. The lymph nodes preferably are removed using imageguidance of the same modality used to detect them.

The invention herein has been described by examples and a particularlydesired way of practicing the invention has been described. However, theinvention as claimed herein is not limited to that specific descriptionin any manner. Furthermore, the features described for one embodimentmay be combined with other embodiments herein disclosed. Equivalence tothe description as hereinafter claimed is considered to be within thescope of protection of this patent.

1-225. (canceled)
 226. A subcutaneous cavity marking devicepercutaneously implantable in breast tissue during a biopsy procedurecomprising: at least two implantable bodies, one made from a firstmaterial and another made from a second material wherein the first andsecond materials are different materials and the at least twoimplantable bodies are adapted to be inserted into a subcutaneous cavitycreated by removal of tissue, wherein the at least two implantablebodies are detectable via non-invasive techniques as tissue cavitymarkers; and at least one of the at least two detectable bodies is anelectronic chip connected to the other of the at least two implantablebodies.
 227. The device of claim 226 wherein the electronic chip isdisposed within the other of the at least two implantable bodies. 228.The device of claim 226 wherein the other of the at least twoimplantable bodies is bioabsorbable.
 229. The device of claim 227wherein the other of the at least two implantable bodies isbioabsorbable.
 230. The device of claim 228 wherein the electronic chipis disposed within the other of the at least two implantable bodies.231. The device of claim 226 wherein the other of the at least twoimplantable bodies is radiopaque.
 232. The device of claim 226 whereinthe other of the at least two implantable bodies is echogenic.
 233. Thedevice of claim 226 wherein the electronic chip is remotelyprogrammable.
 234. The device of claim 233 wherein the information canbe added after implantation of the electronic chip.
 235. The device ofclaim 226 wherein the information is directly encoded into theelectronic chip.
 236. The device of claim 226 wherein the information isa code keyed to a corresponding record in a database.
 237. The device ofclaim 226 wherein the information is a pathology report.
 238. Asubcutaneous cavity marking device percutaneously implantable in breasttissue during a biopsy procedure, the device comprising: a bodydetectable by at least one of x-ray and ultrasound; and an electronicchip, wherein the electronic chip provides information that can beremotely detected.
 239. The device of claim 238 wherein the electronicchip is remotely programmable.
 240. The device of claim 239 wherein theinformation can be added after implantation of the electronic chip. 241.The device of claim 238 wherein the information is directly encoded intothe electronic chip.
 242. The device of claim 238 wherein theinformation is a code keyed to a corresponding record in a database.243. The device of claim 238 wherein the information is a pathologyreport.
 244. A method of marking a biopsy site comprising: disposing anelectronic device in a biopsy cavity; and remotely detecting informationfrom the electronic device.